The Gut Microbiome and the Brain - Galland

[Bob]

I'm placing this in the ME/CFS research section because it specifically refers to chronic fatigue syndrome & fibromyalgia in the abstract.

The Gut Microbiome and the Brain
Galland L.
J Med Food. 2014 Nov 17. [Epub ahead of print]
doi:10.1089/jmf.2014.7000
http://www.ncbi.nlm.nih.gov/pubmed/25402818
http://online.liebertpub.com/doi/abs/10.1089/jmf.2014.7000

Abstract
Abstract The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics.

 

[Simon]

Probably worth noting that the author, Leo Galland, runs the Foundation for Integrated Medicine

Integrated Medicine couples the latest scientific advances with the most profound insights of ancient healing systems, giving you the best ways to preserve health, increase longevity and speed recovery from illness.

So it sounds like a really interesting review and discusses a lot of stuff I've come across elsewhere, but I'm always a bit suspicious when someone writes books like Power Healing: Use the New Integrated Medicine to Cure Yourself

 

[dan062]

" Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome."

This is fascinating.

Am I correct in saying that trying to identify exactly the dysbiotic state that is proposed to drive this in CFS/ME is the rationale for Lipkin's study?

And that if the hypothesis is correct (dysbiosis directly triggering vagal inflammation --> CNS inflammation) that it represents a subtle but importance difference to Van Elzakker's theory which proposes direct infection of the vagal tissue by a pathogen? (Or CNS infection, depending on your understanding).

Anyone know the source for the first idea in the quote (that dysbiosis can have a direct inflammatory effect on the vagal nerve?)

 

[Bob]

" Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome."

Am I correct in saying that trying to identify exactly the dysbiotic state that is proposed to drive this in CFS/ME is the rationale for Lipkin's study?

I'm not sure if Lipkin would necessarily subscribe to everything in this review paper, including the vagal nerve inflammation theory, but, yes, Lipkin is looking for anything unusual in the gut, in terms of microbial populations, and individual microbes. He also intends to look for immune reactions (i.e. antibodies and cytokine patterns) that might correlate to any unusual gut microbe populations in individual patients. And in related research he's carrying out metabolomic and proteomic studies to look for further abnormalities.

So, I think it's correct to say that Lipkin is "trying to identify exactly the dysbiotic state that is proposed to drive this in CFS/ME." To my understanding, he's not chasing the vagal nerve theory specifically, or at least he's never mentioned it as far as I'm aware.

 

[Bob]

And that if the hypothesis is correct (dysbiosis directly triggering vagal inflammation --> CNS inflammation) that it represents a subtle but importance difference to Van Elzakker's theory which proposes direct infection of the vagal tissue by a pathogen? (Or CNS infection, depending on your understanding).

It does seem that way, doesn't it. Galland is talking about gut microbe metabolites interfering with the nervous system (including stimulation of the vagal nerve), rather than direct infection of the nervous system.

 

[adreno]

Right, sending signals through the vagus nerve is different from intrinsic inflammation/infection of the nerve.

 

[Gijs]

One is looking for the presence of poor or certain bacteria in the gut. Maybe they must look at the absence of certain bacteria in the gut!

 

[Bob]

One is looking for the presence of poor or certain bacteria in the gut. Maybe they must look at the absence of certain bacteria in the gut!

Good point. Research needs to look to see if there is an altered or unusual gut microbiome, including if there is an absence of, or low levels of, certain bacteria.

Or it could perhaps even be the case that the gut microbiome is normal in ME patients but the immune system mounts an unusual immune response to certain gut microbes.

I wonder if perhaps the immune system in ME patients is mounting an unusual immune response to certain gut bacteria, whereby ME patients might have high levels of antibodies to certain gut bacteria, and lower levels of those bacteriain the gut compared to healthy controls. (i.e. there is an unusual hyperactive immune response to certain gut bacteria that don't usually provide a strong immune response.)

Alternatively, perhaps gut microbes are escaping into the blood of ME patients via a leaky gut, but the body isn't successfully dealing with those microbes perhaps because we've evolved not to mount an excessive immune response to symbiotic gut bacteria. And there are no unusually high levels of antibodies to those bacteria, despite a leaky gut, because the immune system has not mounted a successful immune response.

Our perhaps a leaky gut is causing an appropriate massive immune response, to the leaky gut, in ME patients, but the body is simply unable to deal with the problem or heal the gut, so the immune response persists.

So many possibilities.

 

[dan062]

Right, sending signals through the vagus nerve is different from intrinsic inflammation/infection of the nerve.

I think there's a very big difference, with pretty profound implications, as Van Elzakker has been saying that directly treating an infection of the vagus would be extremely difficult at present (hence if the hypothesis is correct his suggestion, treatment wise, is focusing on suppressing the microglial response).

 

[Lou]

If it's been overlooked some of you might be interested in the thread, 'Resistant Starch Challenge: Is it the Key We've been looking for?' A few here have already benefitted by taking certain prebiotics to modify the gut.

 

[natasa778]

Good point. Research needs to look to see if there is an altered or unusual gut microbiome, including if there is an absence of, or low levels of, certain bacteria.

Or it could perhaps even be the case that the gut microbiome is normal in ME patients but the immune system mounts an unusual immune response to certain gut microbes.

A gut microbiome researcher recently commented about the whole field changing at the moment, moving away from looking at exact composition of bacteria - as in what individual bacteria are there and what is 'missing' -- and moving towards looking at the effects of each microbiome almost as a living entity (think Gaia Earth). The diversity of each person's microbiome, your ecosystem, and how it is affecting, and is affected by (or controlled by), other body systems being what is important. It is becoming increasingly hard to get/justify funding for looking at individual bacterial absence/presence/levels as they now reckon it cannot tell us very much. One reason being that there are such huge differences in gut microbiome composition between individuals, even perfecly health ones, that it is almost impossible to classify a 'healthy' microbiome.

Metabolomics is predicted to bring more useful answers, and is thankfully becoming faster and more affordable. Then of course there is the whole universe of issues related to (misdirected?) immune responses, intestinal permeability (endotoxins in the blood?), enteric/vagal hypersensitivity etc.

I totally agree with the rest of your post

 

[natasa778]

She says it better here
http://www.thirdagelearningguelph.ca/uploads/7/1/5/5/7155034/guelph_tal_vercoe.pdf (summarised in slides 19-21)

Another amazing fact is that one of the ladies in slide 40 also had her demetia disappear following the transplant!